PMID- 18685070 OWN - NLM STAT- MEDLINE DCOM- 20081204 LR - 20200930 IS - 0363-6119 (Print) IS - 0363-6119 (Linking) VI - 295 IP - 4 DP - 2008 Oct TI - BDNF-TrkB signaling interacts with the GABAergic system to inhibit rhythmic swallowing in the rat. PG - R1050-9 LID - 10.1152/ajpregu.90407.2008 [doi] AB - Brain-derived neurotrophic factor (BDNF) acts as an anorexigenic factor in the dorsal vagal complex (DVC) of the adult rat brain stem. The DVC contains the premotoneurons controlling swallowing, a motor component of feeding behavior. Although rats with transected midbrain do not seek out food, they are able to swallow and to ingest food. Because BDNF and tropomyosin-related kinase B (TrkB) receptors are expressed in the DVC, this study hypothesized that BDNF could modify the activity of premotoneurons involved in swallowing. Repetitive electrical stimulation of the superior laryngeal nerve (SLN) induces rhythmic swallowing that can be recorded with electromyographic electrodes inserted in sublingual muscles. We show that a microinjection of BDNF in the swallowing network induced a rapid, transient, and dose-dependant inhibition of rhythmic swallowing. This BDNF effect appeared to be mediated via TrkB activation, since it no longer occurred when TrkB receptors were antagonized by K-252a. Interestingly, swallowing was inhibited when subthreshold doses of BDNF and GABA were coinjected, suggesting a synergistic interaction between these two signaling substances. Moreover, BDNF no longer had an inhibitory effect on swallowing when coinjected with bicuculline, a GABA(A) receptor antagonist. This blockade of BDNF inhibitory effect on swallowing was reversible, since it reappeared when BDNF was injected 15 min after bicuculline. Finally, we show that stimulation of SLN induced a decrease in BDNF protein within the DVC. Together, our results strongly suggest that BDNF inhibits swallowing via modulation of the GABAergic signaling within the central pattern generator of swallowing. FAU - Bariohay, Bruno AU - Bariohay B AD - Centre de Recherche en Neurobiologie-Neurophysiologie de Marseille, CRN2M, Universite de la Mediterranee, Universite Paul Cezanne, CNRS UMR 6231, USC-INRA 2027, Marseille cedex 20, France. FAU - Tardivel, Catherine AU - Tardivel C FAU - Pio, Juliette AU - Pio J FAU - Jean, Andre AU - Jean A FAU - Felix, Bernadette AU - Felix B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080806 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Enzyme Inhibitors) RN - 0 (GABA-A Receptor Antagonists) RN - 0 (Indole Alkaloids) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - 97161-97-2 (staurosporine aglycone) RN - EC 2.7.10.1 (Receptor, trkB) RN - Y37615DVKC (Bicuculline) SB - IM CIN - Am J Physiol Regul Integr Comp Physiol. 2008 Oct;295(4):R1048-9. PMID: 18753270 MH - Animals MH - Bicuculline/pharmacology MH - Brain Stem/drug effects/physiology MH - Brain-Derived Neurotrophic Factor/pharmacology/*physiology MH - Carbazoles/pharmacology MH - Deglutition/drug effects/*physiology MH - Electric Stimulation MH - Enzyme Inhibitors/pharmacology MH - GABA-A Receptor Antagonists MH - Hypothalamus/drug effects/physiology MH - Indole Alkaloids/pharmacology MH - Laryngeal Nerves/physiology MH - Male MH - Rats MH - Rats, Wistar MH - Receptor, trkB/antagonists & inhibitors/*physiology MH - Signal Transduction/drug effects/*physiology MH - Solitary Nucleus/drug effects/physiology MH - Vagus Nerve/physiology MH - gamma-Aminobutyric Acid/pharmacology/*physiology EDAT- 2008/08/08 09:00 MHDA- 2008/12/17 09:00 CRDT- 2008/08/08 09:00 PHST- 2008/08/08 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/08/08 09:00 [entrez] AID - 90407.2008 [pii] AID - 10.1152/ajpregu.90407.2008 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2008 Oct;295(4):R1050-9. doi: 10.1152/ajpregu.90407.2008. Epub 2008 Aug 6.